Emergence and spread of a new influenza virus have historically caused serious damage to humankind. Even now, a highly pathogenic avian influenza virus is expected to pose large threats when it mutates into a virus capable of human-to-human transmission.
Influenza virus is an enveloped RNA virus and it is categorized into types A, B, and C according to the antigenicity of nucleoprotein (NP) and matrix protein (M). Type A and type B are most common epidemic in human beings.
Even if viruses belong to the same type such as type A, B, or C, they are sub-divided into different serotypes such as H1N1, H5N1, or the like based on difference in antigenicity of hemagglutinin (HA) or neuraminidase (NA), each a molecule on the surface of the envelope.
As an existing anti-influenza drug, zanamivir (Relenza™) (for example, Patent Document 1) and oseltamivir (Tamiflu™) (for example, Patent Document 2) have been used widely.
Zanamivir or oseltamivir suppresses activity of neuraminidase which becomes necessary for infection of an influenza virus from infected cells to other cells. Anti-influenza drugs having another working mechanism include amantadine and rimantadine targeting the matrix protein 2 (M2 protein). They interfere with uncoating of the virus in the infected cells.
Similar to other drugs targeting an enzyme or ion channel, these drugs that inhibit the function of neuraminidase or M2 protein have been developed through derivatization from a substrate, molecular designing based on a steric structure, or discovery of a function from existing compounds. They therefore belong to an analog of a molecule present in a living body or a chemically prepared low molecule.
M2 protein Inhibitors are however effective only for influenza type A and neuraminidase inhibitors do not have efficacy against neuraminidase-free influenza type C.
Anti-viral drugs generally have a limit in its efficacy against viruses that have mutated and therefore acquired resistance to the drugs. Emergence of viruses resistant to popularly used anti-influenza virus drugs such as zanamivir, oseltamivir, and amantadine has also been found. Viruses acquire resistance to anti-viral drugs because of deterioration in affinity of the drugs for a target molecule due to mutation thereof and further, recovery of proliferation potency brought by mutation of another molecule, which is an indirect mechanism. It is therefore difficult to create a drug capable of completely preventing acquisition of resistance for a long period of time.
The present inventors have already found a peptide exhibiting inhibitory activity against influenza viruses by binding to hemagglutinin (Patent Document 3).